The additive erectile recovery effect of brain-derived neurotrophic factor combined with vascular endothelial growth factor in a rat model of neurogenic impotence

OBJECTIVE: To test the hypothesis that combined intracavernosal injection with vascular endothelial growth factor (VEGF) with adeno-associated virus-mediated brain-derived neurotrophic factor (AAV-BDNF) synergistically facilitates the neural regeneration and erectile function after cavernosal nerve injury. MATERIALS AND METHODS: Forty Sprague-Dawley male rats were randomly divided into five equal groups: eight had a sham operation while 32 had bilateral cavernosal nerve freezing followed by an immediate intracavernosal injection with either phosphate-buffered saline (PBS), VEGF, AAV-BDNF, or AAV-BDNF + VEGF. Erectile function was assessed by cavernosal nerve electrostimulation at 3 months, and samples of the major pelvic ganglia and penile tissue were evaluated histologically. RESULTS: In this animal model of impotence from nerve injury, the recovery of erectile function was greatest in those receiving AAV-BDNF + VEGF; the mean (sd) maximal intracavernosal pressure in this group was 87.2 (20.78) cmH2O, compared with 37.3 (11.39) for VEGF alone and 49.8 (29.58) for AAV-BDNF alone. No erectile dysfunction was identified in the sham group, with a pressure of 100.7 (22.70) cmH2O, while all treatment groups significantly outperformed the PBS (control) group, at 29.3 (13.52) cmH2O. Furthermore, all animals receiving monotherapy or combined treatment had more NADPH-diaphorase-positive nerve fibres than controls but less than in the sham group. CONCLUSION: Bilateral cavernosal nerve freezing causes erectile dysfunction with accompanying neurological changes. Intracavernosal injection with either VEGF or AAV-BDNF alone enhances nerve regeneration, with combined therapy (VEGF and AAV-BDNF) promoting neural and erectile recovery additively.     

Use of laboratory toxicity tests with bivalve and echinoderm embryos to evaluate the bioavailability of copper in San Diego Bay, California, USA

Copper concentrations in parts of San Diego Bay (CA, USA) exceed ambient water quality criteria (WQC; currently 3.1 microg/L dissolved, U.S. Environmental Protection Agency [U.S. EPA]). In order to better understand the bioavailability of copper to water-column organisms in the bay, toxicity tests were performed with copper added to surface water collected from various sites in the estuary over a three-year period. The species and endpoints used, bivalve and echinoderm embryo-larval development, are among the most sensitive in the U.S. EPA's national toxicity dataset, which is used to derive WQC. No toxicity was observed in ambient bay water samples, as indicated by high proportions of normally developed larvae in control treatments, averaging 93+/-5% across all sites and all sampling events. Median effects concentrations (EC50), obtained by copper spiking of ambient water samples, ranged from 1.7 to 3.4 times lower at sites located near the mouth compared to sites near the back of the bay. These data indicate a gradient in complexation capacity increasing from the mouth to the back of the bay, which is consistent with similar trends in dissolved organic carbon and total suspended solids. For the bay as a whole, estimates for total recoverable and dissolved water-effect ratios (WER) ranged from 2.07 to 2.27 and 1.54 to 1.67, respectively. Water-effect ratios of this magnitude suggest that adoption of a somewhat higher site-specific WQC for San Diego Bay still would achieve the level of protection that is intended by the WQC guidelines.     

Assessing reliable and clinically significant change on Health of the Nation Outcome Scales: method for displaying longitudinal data

OBJECTIVE: Many authors recommended that reliable and clinically significant change (RCSC) should be calculated when reporting results of interventions. To test the reliability of the Health of the Nation Outcome Scales (HoNOS) in identifying RCSC, we applied the Jacobson and Truax model to two HoNOS assessments in a large group of people evaluated in 10 community mental health services in Lombardy, Italy, in 2000. METHOD: The HoNOS was administered to 9817 patients; of these, 4759 (48%) were re-assessed. Reliable change (RC) was calculated using Cronbach's alpha (alpha), as a parameter of the reliability of the measure. Clinical significance cut-offs were calculated using a classification of severity based on HoNOS items. RESULTS: In the whole sample, the clinical improvement cut-off was 11 and the remission cut-off was 5. Considering the severe patients, the clinical improvement cut-off was 12. The RC index calculated on the whole group and on the subgroup of severe patients indicated that eight-point and seven-point changes, respectively, were needed to be confident that a real change had occurred. Longitudinal changes were depicted on two-dimensional graphs as examples of reporting RCSC on HoNOS total scores in a routine data collection: 91.6% of the whole sample (4361) was stable, 5.6% (269) improved and 1.8% (129) worsened. CONCLUSION: Our study proposes a methodological framework for computing RCSC normative data on a widely used outcome scale and for identifying different degrees of clinical change.     

Thrombosed cavernous hemangioma of the anterior mediastinum. A report of one case

Mediastinum hemangioma is a rare benign tumor. We performed surgery and present the first reported case in Chile. The patient is a 24-year-old symptomatic woman, referred to our hospital from a rural health center. The patient had all routine preoperative studies, chest radiographs and computed tomography of the thorax. We performed a median sternotomy with a complete resection of the mass. During the 36-month follow-up, she was well, asymptomatic and without relapse evidence. A review of the most outstanding characteristics of this rare tumor is presented.     

In vitro culture of rat neuromicrovascular endothelial cells on polymeric scaffolds

Polyphosphazenes are polymers possessing a skeleton composed of alternating phosphorous and nitrogen atoms, and two side-moieties linked to each phosphorous atom. Polyphosphazenes with amino acid esters as side-moieties are biocompatible and biodegradable polymers. Two polyphosphazenes, poly[bis(ethyl alanate) phosphazene] and poly[(ethyl phenylalanate)0.8(ethyl alanate)0.8(ethyl glycinate)0.4 phosphazene] (PPAGP) were synthesized, and processed to form small fibers. Their ability to support rat neuromicrovascular endothelial cell (EC) adhesion and growth has been studied, using poly(D,L-lactic acid) as reference compound. Scanning electron microscopy revealed that both poly[bis(ethyl alanate) phosphazene] and PPAGP fibers were thinner than poly(D,L-lactic acid) fibers, and possessed a more irregular and porous surface. All polymers increased EC adhesion, compared with polystyrene, but only polyphosphazenes were able to improve EC growth. The highest increase in EC proliferation was induced by PPAGP, which, as revealed by environmental scanning electron microscopy, was also able to induce ECs to arrange into tubular structures. The conclusion is drawn that PPAGP may provide the best scaffold for engineered blood vessels, because it promotes adhesion, growth, and organization of ECs into capillary-like structures.     

Parental bonding: a key factor for mental health of college women

The purpose of this study was to investigate the relationship of parental bonding to the mental health of college women aged 18 to 24 years. A cross-sectional study of a volunteer sample of 246 college women was conducted. Data on depressive symptoms, negative thinking, self-esteem, and parental bonding were collected via self-report. Maternal care was the strongest predictor of all four mental health indices. Paternal overprotection predicted scores of three of the four mental health measures. Women with optimal maternal and paternal bonding profiles (high care/low overprotection) had fewer depressive symptoms, less negative thinking, and higher self-esteem than women with other bonding profiles. The findings have implications for prevention, screening, and intervention to enhance the mental health of college women.     

Cloned horse pregnancies produced using adult cumulus cells

The objectives of the present study were to: (1) clone horses using adult cumulus cells; and (2) determine whether the cumulus cell donor affected the outcome. In vivo-matured cumulus-oocyte complexes were obtained using transvaginal ultrasound-guided follicle aspiration; oocytes were used as cytoplasts, whereas cumulus cells (from one of three different mares) were used as donor cells. Immediately following nuclear transfer and activation procedures, cloned embryos were transferred surgically to the oviduct of recipient mares (n = 2-5 embryos per recipient) that had ovulated within 24 h prior to the transfer. An initial pregnancy examination was performed between Days 14 and 16 (Day 0 = surgery); subsequent examinations were then performed every 7-10 days. A total of 136 follicles were aspirated in 96 mares, from which 72 oocytes were recovered (53%). Sixty-two cloned embryos were transferred to recipient mares, which resulted in seven (11.3%) ultrasonographically detectable conceptuses between Days 14 and 16. All seven conceptuses were lost spontaneously between Days 16 and 80. Cumulus cells from Mare 160 tended (P = 0.08) to result in a higher embryo survival rate than cumulus cells from Mare 221 (4/17 v. 1/25 respectively). To our knowledge, this is the first report documenting the establishment of cloned equine pregnancies derived from adult cumulus cells.     

Deficit of in vivo mitochondrial ATP production in OPA1-related dominant optic atrophy

Dominant optic atrophy has been associated with mutations in the OPA1 gene, which encodes for a dynamin-related GTPase, a mitochondrial protein implicated in the formation and maintenance of mitochondrial network and morphology. We used phosphorus magnetic resonance spectroscopy to assess calf muscle oxidative metabolism in six patients from two unrelated families carrying the c.2708-2711delTTAG deletion in exon 27 of the OPA1 gene. The rate of postexercise phosphocreatine resynthesis, a measure of mitochondrial adenosine triphosphate production rate, was significantly delayed in the patients. Our in vivo results show for the first time to our knowledge a deficit of oxidative phosphorylation in OPA1-related DOA.     

VEGF-mediated inflammation precedes angiogenesis in adult brain

Vascular endothelial growth factor (VEGF) has been shown to induce angiogenesis when infused continuously into adult rat brain tissue. In addition, VEGF has been shown to enhance permeability in brain vasculature. Adult rats were continuously infused with mouse VEGF into neocortex for up to 7 days. We studied the development of VEGF-induced vasculature in rat neocortex and evaluated the temporal expression of a wide variety of markers for inflammation and vascular leak in relation to the angiogenic response using immunohistochemistry and Western blot analysis. We report here that VEGF-mediated inflammation in brain is characterized by upregulation of ICAM-1 and the chemokine MIP-1alpha, as well as a preferential extravasation of monocytes. VEGF causes a dramatic breakdown of the blood-brain barrier, which is characterized by decreased investment of the vasculature with astroglial endfeet. Perivascular cells, in contrast, increase around the newly formed cerebrovasculature. In addition, breakdown of the blood-brain barrier, leukocyte extravasation, and extracellular matrix deposition occur before vascular proliferation. Furthermore, administration of low doses of VEGF induces permeability and inflammation without appreciable vascular proliferation.